Erschienen in:
01.12.2005 | Short Communication
D6S265*15 marks a DRB1*15, DQB1*0602 haplotype associated with attenuated protection from type 1 diabetes mellitus
verfasst von:
A. M. Valdes, G. Thomson, J. Graham, M. Zarghami, B. McNeney, I. Kockum, A. Smith, M. Lathrop, A. R. Steenkiste, J. S. Dorman, J. A. Noble, J. A. Hansen, A. Pugliese, Å. Lernmark, Swedish Childhood Study Group, Diabetes Incidence in Sweden Study Group, Type 1 Diabetes Component of the 13th International Histocompatibility Working Group
Erschienen in:
Diabetologia
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Ausgabe 12/2005
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Abstract
Aims/hypothesis
The HLA class II DQB1*0602 allele confers strong dominant protection against type 1 diabetes but protection is not absolute. The aim of this study was to identify markers within the HLA region that differentiate DQB1*0602 haplotypes and show different associations with disease risk.
Methods
We defined alleles at eight microsatellite markers spanning the HLA region in a case-control cohort from Sweden.
Results
We found that allele 15 at marker D6S265 (109 kb centromeric of HLA-A) was over-represented among patients carrying DRB1*15, DQB1*0602. A detailed haplotype analysis showed that DRB1*15, DQB1*0602 haplotypes carrying D6S265*15 have a ten-fold higher odds ratio (OR) than those carrying other alleles and thus confer reduced protection [OR D6S265*15=0.186 (95% CI 0.074, 0.472) vs OR D6S265*15−=0.017 (95% CI 0.005, 0.062), p<0.001].
Conclusions/interpretation
Our data support the existence of a locus that modifies the protective effect associated with DQB1*0602. Typing for allele D6S265*15 can identify a less protective DQB1*0602 haplotype, thereby allowing a more accurate prediction of type 1 diabetes risk.